RNA-sequencing of a mouse-model of spinal muscular atrophy reveals tissue-wide changes in splicing of U12-dependent introns

Spinal Muscular Atrophy (SMA) is a neuromuscular disorder caused by insufficient levels of the Survival of Motor Neuron (SMN) protein. SMN is expressed ubiquitously and functions in RNA processing pathways that include trafficking of mRNA and assembly of snRNP complexes. Importantly, SMA severity is correlated with decreased snRNP assembly activity. In particular, the minor spliceosomal snRNPs are affected, and some U12-dependent introns have been reported to be aberrantly spliced in patient cells and animal models. SMA is characterized by loss of motor neurons, but the underlying mechanism is largely unknown. It is likely that aberrant splicing of genes expressed in motor neurons is involved in SMA pathogenesis, but increasing evidence indicates that pathologies also exist in other tissues. We present here a comprehensive RNA-seq study that covers multiple tissues in an SMA mouse model. We show elevated U12-intron retention in all examined tissues from SMA mice, and that U12-dependent intron retention is induced upon siRNA knock-down of SMN in HeLa cells. Furthermore, we show that retention of U12-dependent introns is mitigated by ASO treatment of SMA mice and that many transcriptional changes are reversed. Finally, we report on missplicing of several Ca2+ channel genes that may explain disrupted Ca2+ homeostasis in SMA and activation of Cdk5

Utility of clinical-epidemiological profiles in outbreaks of foodborne disease, Catalonia, 2002 through 2006

The objective of this study was to evaluate the use of clinical- epidemiological profiles for classifying non-laboratory-confirmed outbreaks of foodborne disease (FBD) in Catalonia between 2002 and 2006 and for elucidating associations among factors contributing to these outbreaks. A total of 275 nonfamily outbreaks were studied, of which 190 (69.1%) were laboratory confirmed and 85 (30.9%) were not. In 176 (92.6%) of laboratory-confirmed outbreaks and 69 (81.2%) of non-laboratory-confirmed outbreaks, information was obtained on contributing factors (P = 0.009). In 72% of non-laboratory-confirmed outbreaks, the etiology was assigned by using clinical-epidemiological profiles; thus, 93% of outbreaks eventually were associated with an etiology. In laboratory-confirmed outbreaks, poor personal hygiene was positively associated with norovirus (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.47 to 4.89; P = 0,0007) and negatively associated with Salmonella and Campylobacter (OR, 0.54; 95% CI, 0.33 to 0.89; P = 0.01), and an unsafe source was positively associated with Salmonella and Campylobacter (OR, 4.07; 95% CI, 1.72 to 10.09; P = 0.001) and negatively associated with norovirus (OR, 0.14; 95% CI, 0.04 to 0.58; P = 0.001). No differences were found among contributing factors associated with outbreaks with a laboratoryconfirmed etiology and those associated with outbreaks with an etiology assigned according to the clinical-epidemiological profiles. Clinical-epidemiological profiles are useful for determining what prevention and control strategies are appropriate to the agents involved in each community and for designing outbreak investigations. Copyright ©, International Association for Food Protection.This work was partially funded by the Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain, and by the Fondo de Investigaciones Sanitarias (project PI 030877).Peer Reviewe

Empirical Research on Sovereign Debt and Default

The long history of sovereign debt and the associated enforcement problem have attracted researchers in many fields. In this paper, we survey empirical work by economists, historians, and political scientists. As we review the empirical literature, we emphasize parallel developments in the theory of sovereign debt. One major theme emerges. Although recent research has sought to balance theoretical and empirical considerations, there remains a gap between theories of sovereign debt and the data used to test them. We recommend a number of steps that researchers can take to improve the correspondence between theory and data

The State Dependent Impact of Bank Exposure on Sovereign Risk

The theoretical literature remains inconclusive on whether changes in bank exposure towards the domestic sovereign have an adverse effect on the sovereign risk position via a diabolic loop in the sovereign-bank nexus or reduce perceived default risk by acting as a disciplinary device for the sovereign. In this paper we empirically analyze the impact of exogenous changes in bank exposure on the risk position of the sovereign within a Markov switching structural vector autoregressive in heteroscedasticity (MSH-SVAR) framework for a set of EMU countries. We add to the methodological literature by allowing for regime dependent shock transmissions according to the volatility state of the financial system. Finding support for both, a stabilizing and a destabilizing effect, we document a clear clustering among the country sample: Rising bank exposure increased default risk for the EMU periphery, but decreased credit risk for the core EMU countries during times of financial stress

Capital Flow Waves to and from Switzerland before and after the Financial Crisis

This paper first shows that capital inflows to and outflows from financial centres were disproportionately affected by the global financial crisis. Switzerland was no exception. The paper then identifies waves of capital flows to and from Switzerland from 2000:Q1 to 2014:Q2 by using a simple statistical method. The analysis shows that private capital inflows to and outflows from Switzerland have become exceptionally muted and less volatile since the crisis. Further, strong and long-lasting "home bias" behaviour can be observed for both Swiss and foreign investors. By contrast, net private capital flows have shown significantly higher volatility since the financial crisis, frequently registering extreme movements driven by extreme movements in bank lending flows. These findings suggest that the financial crisis generated a breaking point for capital flows to and from Switzerland

Structural Volatility in Mexico: A Policy Report

This paper surveys Mexico`s economic weaknesses and provides related policy recommendations. Current problems include weak international financial links and external conditions, a recurrent credit crunch and financial underdevelopment problem, with particularly fragile banks, a weak fiscal situation, due to extreme vulnerability to internal and external shocks, and a latent monetary policy credibility problem. The paper`s policy recommendations include improving external financial links, reducing direct exposure to external shocks, accelerating domestic financial deepening and strengthening existing arrangements, reducing public accounts exposure to internal and external shocks, and stabilizing very high and very low frequency movements in the nominal exchange rate

Factors Associated to Duration of Hepatitis A Outbreaks: Implications for Control

Even though hepatitis A mass vaccination effectiveness is high, outbreaks continue to occur. The aim of this study was to investigate the association between duration and characteristics of hepatitis A outbreaks. Hepatitis A (HA) outbreaks reported between 1991 and 2007 were studied. An outbreak was defined as ≥2 epidemiologically-linked cases with ≥1 case laboratory-confirmed by detection of HA immunoglobulin M (IgM) antibodies. Relationships between explanatory variables and outbreak duration were assessed by logistic regression. During the study period, 268 outbreaks (rate 2.45 per million persons-year) and 1396 cases (rate 1.28 per 105 persons-year) were reported. Factors associated with shorter duration were time to intervention (OR = 0.96; 95% CI: 0.94–0.98) and school setting (OR = 0.39; 95% CI: 0.16–0.92). In person-to-person transmission outbreaks only time to intervention was associated with shorter outbreak duration (OR = 0.96; 95% CI: 0.95–0.98). The only variables associated with shorter outbreak duration were early administration of IG or vaccine and a school setting. Timely reporting HA outbreaks was associated with outbreak duration. Making confirmed HA infections statutory reportable for clinical laboratories could diminish outbreak duration

What Drives Different Types of Capital Flows and their Volatilities in Developing Asia?

Understanding the determinants of capital inflows is essential to designing an effective policy framework to manage volatile capital flows and their disruptive potential. This paper aims to identify factors that explain the size and volatility of various types of capital flows to developing Asia, vis-à-vis other emerging market economies. The estimates for a panel dataset show that per capita income growth, trade openness, and change in stock market capitalization are important determinants of capital inflows to developing Asia. Trade openness increases the volatility of all types of capital inflows; while change in stock market capitalization, global liquidity growth and institutional quality lowers the volatility. A regional factor plays an important role in determining the size and volatility of capital inflows in emerging Europe and emerging Latin America, suggesting that regional economic cooperation and policy coordination may be an important element in designing a policy framework to manage capital inflows